This is a renewal request to continue studies of lipid metabolism and the effects of prolonged ethanol intake. Studies of hepatic glycerolipid biosynthesis and its regulation are directed to a description of the enzymatic reactions in this pathway with attention to substrate specificity, reaction products and cofactors. The effects of environmental factors including hormonal state, nutrition, ethanol and drugs on the activity of this pathway and the individual reactions will be studied. Changes in this pathway will be correlated with hepatic and serum lipid concentrations. The effects of prolonged ethanol ingestion on hepatic phospholipid metabolism, structure and function of the endoplasmic reticulum and the drug metabolizing enzymes will be measured. The mechanism of ethanol induced increases and decreases in the activity of the enzymes of drug metabolism will be studied further.